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Biomedical subjects

J Kagan

Publications and source records attributed to J Kagan.

At least 73 records · Page 4Linked to original sources
PubMed1994

Photosensitized cross-linking and cleavage of pBR322 and M13 DNA: comparison of 4,4',6-trimethylangelicin and 3-carbethoxypsoralen.

The furocourmarins 3-carbethoxypsoralen (3-CP) and 4,4',6-trimethylangelicin (TMA) were generally believed to be incapable of cross-linking DNA upon irradiation with ultraviolet light. Denaturation of photosensitized pBR322 DNA, either supercoiled or previously linearized with a restriction enzyme, proved that 3-CP was indeed monofunctional, but that TMA produced cross-links. Identical conclusions were reached with double stranded M13 DNA which had been linearized with EcoR 1. Both sensitizers also induced partial DNA cleavage. In contrast to 3-CP, photosensitization with TMA made the DNA resistant to enzymatic cleavage.

Bacteriophage M13↗
PubMed1994

Crosslinking and cleavage of pBR322 DNA photosensitized by 7-methylpyrido[3,4-c]psoralen.

7-Methylpyrido[3,4-c]psoralen (7-MPP) had been designed to be a monofunctional sensitizer in which the pyrone double bond, being engaged in a pyridine ring, would be incapable of participating in the formation of a cyclobutane ring with a DNA component. However, one example of photosensitization of thymine-thymine dimer formation in DNA by 7-MPP had been reported. This paper proves that 7-MPP can sensitize interstrand crosslinks in pBR322 DNA. It also proves that 7-MPP photosensitizes double strand cleavage reactions in the DNA with an unusually large degree of site selectivity.

Carcinogens↗
PubMed1994

The role of microsomal mixed function oxidases in the metabolism and mechanism of action of certain organophosphorus insecticides.

The influence of microsomal mixed function oxidases (MFO) on the biotransformation of pesticides was investigated in experiments with perfusion of isolated rat livers and in whole animals. The pesticides examined were 3 organophosphorus insecticides (OP): S-propyl-O-phenyl-O-ethylthiophosphate (heterophos), a mixture of O,O-dimethyl-O-cyclohexylthionphosphate and O,S-dimethyl-O-cyclohexylthiolphosphate (cyclophos), and dithiophosphonate. The indices of NADPH-dependent hydroxylating systems measured in the microsomal fraction of rat liver homogenates were the activity of aniline hydroxylase, aminopyrine demethylase and the amount of cytochrome P-450. It was shown that not only did the specific chemical structure of the OP and induction or inhibition of MFO determine OP activation and detoxification (and thus its biological action), but also the route and frequency of exposure could influence these parameters.

Animals↗
PubMed1994

On the nature of emotion.

This essay has tried to make three points. First, humans are capable of a large number of affect states (the exact number is not yet known), each marked by a distinct profile of physiology, cognition, and behavior, and each requiring a distinct name. Second, a distinction should be made among acute emotions, chronic moods, and temperamental vulnerabilities to a particular emotion state. Finally, research on human affects will profit from a return to, and a reinterpretation of, Freud's suggestion of unconscious affect states. Such inquiry would provide a corrective to the current reliance on the verbal reports of phenomenal states on questionnaires or in interviews as either the only, or the primary, index of an emotion. Continued use of this strategy will limit analyses to a small number of heterogeneous states that happen to have a popular English name and will retard discovery of the larger number of affect states that are of significance for human function. Discovery of these states will require use of new sources of evidence to supplement popular ones, including facial and postural expressions, muscle tension, EEG, vagal tone, heart-rate changes, blood pressure, GSR, facial temperature, and blood or saliva indexes of norepinephrine, opioids, and cortisol. When the cosmologist James Peebles was asked to guess the exact numerical answers to a series of astronomical puzzles, like the age of the universe or of a distant star, he replied, "If someone gave me on a tablet of clay the answer and the numbers, I would be disappointed. I would throw it away because the great discoveries are not going to be a final number, but the method you come to apply to learn that number."

Adaptation, Psychological↗
PubMed1993

Assessment of the effects of instrumentation, monoclonal antibody, and fluorochrome on flow cytometric immunophenotyping: a report based on 2 years of the NIAID DAIDS flow cytometry quality assessment program.

This study of the effect on CD4%, CD8%, CD3+8+%, and CD3% of flow cytometer, monoclonal antibody, and fluorochrome was based on 71 whole-blood samples, each evaluated by 42 to 59 laboratories during 2 years of a flow cytometry quality assessment program. For the 24 HIV-positive specimens, FACScans produced significantly lower CD4% values than EPICS-Cs or EPICS Profiles, and for the 47 HIV-negative specimens, FITC was associated with significantly lower CD4% values than PE or RD1, but differences were never larger than 2% and regressions accounted for only 3-12% of the variability. The labs using the most common CD4 technique had significantly higher between-laboratory variability than all other labs grouped together. For both CD8 and CD3+8+, measurements on FACScans were significantly higher than measurements on EPICS, and measurements using Leu2 were significantly higher than measurements using T8, with regressions accounting for 12-31% of the variability. The machine differences in medians were 3-7% for labs using Leu2-FITC. It might be worthwhile to discourage the use of Leu2-FITC for measuring CD8% but no change in instrument, monoclonal antibody, or fluorochrome would greatly improve interlaboratory agreement on CD4%.

Antibodies, Monoclonal↗
PubMed1993

Photosensitized cleavage and cross-linking of pBR322 DNA with khellin and visnagin.

The naturally occurring furanochromones khellin and visnagin have received considerable attention, largely because of their vasodilatory properties and of their ability (particularly that of khellin) to induce skin pigmentation upon ultraviolet light treatment of patients suffering from vitiligo. There are conflicting statements in the literature on whether or not they are capable of cross-linking DNA photochemically. Supercoiled and linear pBR322 DNA was used to probe this reaction. The results showed that both khellin and, to a greater extent, visnagin photosensitized DNA cross-linking. In addition, both photosensitizers induced extensive DNA cleavage.

Cross-Linking Reagents↗
PubMed1993

DNA cleavage, antiviral and cytotoxic reactions photosensitized by simple enediyne compounds.

Very potent antibiotic antitumor natural products contain a enediyne moiety which, upon thermal activation, is capable of abstracting hydrogens from DNA. 1,6-Diphenyl-3-hexene-1,5-diyne was selected as a candidate for inducing DNA strand breaks photochemically. Easily interconverted with light, both geometric isomers 1 and 2 were expected to be phototoxic. As anticipated, they photosensitized the production of strand breaks in double-stranded supercoiled pBR322, and in single-stranded M13 DNA. The DNA cleavage reactions were favored by the presence of oxygen and were inhibited by ethanol. Preliminary experiments with the (Z)-isomer indicated moderate light-dependent antiviral activity against human immunodeficiency virus (HIV), Sindbis virus, and mouse cytomegalovirus. The enediynes were cytotoxic to Escherichia coli, a gram-negative organism, to Streptococcus faecalis, a gram-positive organism, to Daphnia magna and to fish (Pimephales promelas), but only in the presence of light. The production of o-terphenyl, the expected product of Bergman cyclization of 1, could not be confirmed. However, both 1 and 2 photosensitized the formation of singlet oxygen and of superoxide anion radical, and photodynamic reactions could have been responsible for some of the phototoxic reactions observed.

3T3 Cells↗
PubMed1993

A 3-year follow-up of children with and without behavioral inhibition.

OBJECTIVE: Previous work suggested that children of parents with panic disorder and agoraphobia were likely to be classified as behaviorally inhibited and that behaviorally inhibited children were likely to develop anxiety disorders. Although these findings suggested that "behavioral inhibition to the unfamiliar" may be associated with risk for anxiety disorders in children, longitudinal data were needed to confirm the initial impressions. METHOD: Using DSM-III structured interviews, the authors examined psychiatric disorders at 3-year follow-up in children of two independently ascertained, previously described, and preexisting samples of children. One sample was cross sectional and clinically derived (Massachusetts General Hospital at-risk sample), and the other was epidemiologically derived and longitudinal (Kagan et al. Longitudinal Cohort). RESULTS: Analyses of follow-up findings revealed significant differences between inhibited and not inhibited children in the rates of multiple > or = 4 psychiatric disorders, multiple > or = 2 anxiety disorders, avoidant disorder, separation anxiety disorder, and agoraphobia. Among inhibited children, the rates of anxiety disorders increased markedly from baseline to follow-up assessments, attaining statistical significance for multiple > or = 2 anxiety disorders and avoidant disorder. Our findings also show there were significant differences between inhibited and not inhibited children in the emergence of multiple > or = 2 anxiety disorders, avoidant disorder, and separation anxiety disorder in children who did not have these diagnoses at baseline. CONCLUSIONS: These findings indicate that inhibited children are at high risk for developing childhood-onset anxiety disorders and provide additional support for the hypothesis that behavioral inhibition is a predictor of later anxiety disorder.

Adolescent↗
PubMed1993

Phototoxicity of (1H-indenyl)thiophenes.

The (1H-indenyl)thiophene derivatives 2 and 3 were recently reported to be excellent singlet oxygen sensitizers, comparable to alpha-terthienyl (1). The phototoxicity of these compounds was compared, using human erythrocytes, Aedes aegypti mosquito larvae, Daphnia magna, and fish (fathead minnows, Pimephales promelas). The known ranking of the photooxidation properties was found to be a good predictor of phototoxic properties in erythrocytes and mosquito larvae but not in daphnias. All three compounds photosensitized the cleavage of supercoiled pBR322 DNA to the same extent.

Aedes↗
PubMed1993

Genetic change and continuity from fourteen to twenty months: the MacArthur Longitudinal Twin Study.

Genetic change as well as continuity was investigated within the domains of temperament, emotion, and cognition/language for 200 pairs of twins assessed at 14 and 20 months of age in the laboratory and home. The second year of life is marked by change rather than continuity: correlations from 14 to 20 months averaged about .30 for observational measures of temperament and emotion, about .40 for language measures, and about .50 for mental development. 2 types of genetic change were examined: changes in the magnitude of genetic influence (heritability) and genetic contributions to change from 14 to 20 months. In general, heritability estimates were similar at 14 and 20 months. Evidence for genetic influence on change from 14 to 20 months emerged for several measures, implying that heritability cannot be equated with stability. Analyses of continuity indicated that genetic factors are largely responsible for continuity from 14 to 20 months.

Child Development↗
PubMed1993

Advances in the diagnosis of acute leukemia.

The diagnosis and monitoring of acute leukemia requires a multiparameter approach. Although the foundation of diagnosis continues to depend on morphologic and cytochemical determinations, the importance of immunologic, cytogenetic, and molecular classifications is beginning to be emphasized and addressed worldwide. In addition to aiding in the diagnosis of acute leukemia, the information gained by these studies increases the understanding of the pathobiology of these neoplasms.

Acute Disease↗
PubMed1992

Stable behavioral inhibition and its association with anxiety disorder.

"Behavioral inhibition to the unfamiliar" is a temperamental construct reflecting the tendency to be shy, timid, and constrained in novel situations. Previous work has suggested that it may be associated with anxiety disorders in children. Psychopathology was assessed in children from a nonclinical sample originally identified as behaviorally inhibited or uninhibited at 21 months and followed through 7 1/2 years. Children who remained inhibited at 4, 5 1/2 and 7 1/2 years (Stable Inhibited) had higher rates of anxiety disorders than children who were not consistently inhibited. Their parents had higher rates of multiple childhood anxiety disorders and of continuing anxiety disorder. These results suggest that the association between behavioral inhibition and anxiety disorder is accounted for by children who have stable behavioral inhibition.

Anxiety Disorders↗
PubMed1992

Psoralens cleave pBR322 DNA under ultraviolet radiation.

Supercoiled (SC) pBR322 was used to probe the recent claim that 5-geranoxylpsoralen (5-GOP) did not photoreact with DNA. Contrary to expectations, 5-GOP was found to damage DNA in the presence of UV-A through two competing pathways: (a) single strand breaks, identified by the conversion of supercoiled into open circular and linear DNA, and (b) cross-linking, revealed by the fluence-dependent decrease in the extent of denaturation of the double stranded supercoiled DNA to single stranded circular DNA. In addition, a fluence-dependent modification reduced the ability of the restriction enzyme EcoR I to linearize the photosensitized DNA, and alkali-labile lesions were generated. Psoralen, 5-methoxypsoralen, and 8-methoxypsoralen, which are well-known to undergo cycloaddition to DNA, had a more pronounced effect on supercoiled DNA. Single strand breaks occurred more readily than with 5-GOP, and the surviving SC form remaining had reduced electrophoretic mobility in agarose gels. In all cases, the DNA damage was more prominent when oxygen was absent.

DNA, Superhelical↗
PubMed1992

Photosensitization by 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol: damage to erythrocyte membranes, Escherichia coli, and DNA.

The natural product 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol (1) photosensitized the inactivation of Escherichia coli in the presence of near-ultraviolet light (320-400 nm; NUV) under both aerobic and anaerobic conditions. A series of E. coli strains differing in DNA repair capabilities and catalase proficiency exhibited indistinguishable inactivation kinetics following treatment with the chemical plus NUV. The presence of carotenoids did afford some protection to E. coli against inactivation under aerobic conditions, consistent with the involvement of singlet oxygen. The photosensitized hemolysis of human erythrocytes occurred more rapidly in the absence than in the presence of oxygen. Aerobically, the onset of hemolysis was partially inhibited by NaN3 and by 2,6-di-t-butyl-4-methylphenol (BHT) but not by superoxide dismutase (SOD). The aerobic lipid peroxidation observed in the membranes of erythrocyte ghosts was completely inhibited by BHT, and partially by NaN3, but not by SOD. These results suggest that either lipid peroxidation of the membrane is not the main cause of photohemolysis or that BHT has insufficient access to intact erythrocyte lipids to protect them. Aerobically, crosslinking of membrane proteins was also observed; it was not affected by SOD, but was partially inhibited by BHT and NaN3. The anaerobic photosensitized hemolysis of erythrocytes was more rapid; a radical mechanism was suggested since BHT inhibited the hemolysis to a greater extent than under aerobic conditions. Neither lipid peroxidation nor protein crosslinking was observed under conditions believed to be anaerobic. A light-dependent electron transfer to cytochrome c was obtained under argon but not under oxygen. Although induced mutations were not observed in the experiments with E. coli, 1 was capable of damaging both supercoiled pBR322 and Haemophilus influenzae transforming DNA in a manner that seemed to be equivalent under aerobic and anaerobic conditions. In conclusion, 1 can behave as typical photodynamic molecule under aerobic conditions but, in contrast to most photodynamic molecules, it is also phototoxic under anaerobic conditions. The extent to which the radical reactions detected under anaerobic reactions compete with the photodynamic processes when oxygen is present is not known.

Alkadienes↗